TAK1 inhibition in the DFG-out conformation

  • Chem Biol Drug Des. 2013 Nov;82(5):500-5. doi: 10.1111/cbdd.12169.
Iain Kilty  1 ,  Martin P Green ,  Andrew S Bell ,  David G Brown ,  Peter G Dodd ,  Christopher Hewson ,  Samantha J Hughes ,  Christopher Phillips ,  Thomas Ryckmans ,  Robert T Smith ,  Willem P van Hoorn ,  Philip Cohen ,  Lyn H Jones
Affiliations
  • 1. Pfizer World Wide Research and Development, Ramsgate Road, Sandwich, CT13 9NJ, UK; BioTherapeutics Research and Development, Pfizer, Cambridge, MA, 02140, USA.
PMID: 23745990 DOI: 10.1111/cbdd.12169
Abstract

The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.

Keywords
X-ray crystallography; chemical biology; drug design; kinase; phosphatase; structure-based drug design.
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